Although endothelial progenitor cells (EPCs) are considered to be an essential source of vascular endothelial repair, their bidirectional differentiation determines that they play a double-edged role in the restoration of endothelial injury. In this research, we investigated the effect of Kir2.1 ion channel on the transdifferentiation of endothelial progenitor cells (EPCs) under the oscillating shear stress (OSS) and the molecular mechanisms underlying the pathological vascular remodeling. EPCs were treated with OSS (± 3.5 dynes/cm2, 1 Hz) simulated with the parallel flow chamber system. The results have shown that OSS promoted the expression of α-SMA and SM22, markers of mesenchymal cells on EPCs. Moreover, OSS also increased expression of Kir2.1 in EPCs. The down-regulation of Kir2.1 reduced OSS-induced EPC mesenchymal transdifferentiation. The overexpression of Kir2.1 suppressed the angiogenic abilities of EPCs in vitro. In parallel, the overexpression of Kir2.1 on EPCs thickened the carotid tunica intima in rat carotid artery balloon injured model in vivo. Taken together, those data indicated that the OSS could facilitate the transdifferentiation of EPCs by increasing Kir2.1 expression. This study provides a novel insight into the pathogenesis of cardiovascular diseases and gives evidence for Kir2.1 as a potential therapeutic target.

中文翻译：

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振荡的剪切应力通过Kir2.1通道介导EPC的间质转分化。

尽管内皮祖细胞（EPC）被认为是血管内皮修复的重要来源，但它们的双向分化决定了它们在恢复内皮损伤中起着双重作用。在这项研究中，我们研究了Kir2.1离子通道在振荡切应力（OSS）下对内皮祖细胞（EPC）转分化的影响以及病理性血管重塑的分子机制。用平行流室系统模拟的OSS（±3.5达因/ cm2，1 Hz）处理EPC。结果表明，OSS促进了EPC上的间充质细胞标志物α-SMA和SM22的表达。此外，OSS还增加了EPC中Kir2.1的表达。Kir2.1的下调减少了OSS诱导的EPC间充质转分化。Kir2.1的过表达抑制了体外EPC的血管生成能力。同时，体内EPCs上Kir2.1的过度表达使大鼠颈动脉球囊损伤模型中的颈内膜增厚。总体而言，这些数据表明OSS可以通过增加Kir2.1表达来促进EPC的转分化。这项研究为心血管疾病的发病机理提供了新颖的见解，并为Kir2.1作为潜在的治疗靶点提供了证据。